| 1. |
- Masoumi, Zahra, et al.
(author)
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Assessing erythroferrone and iron homeostasis in preeclamptic and normotensive pregnancies : A retrospective study
- 2023
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In: Placenta. - : Elsevier BV. - 0143-4004. ; 133, s. 10-18
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Journal article (peer-reviewed)abstract
- Introduction: Preeclampsia (PE) is a pregnancy-related disorder associated with maternal hypertension and placental dysfunction. A significant micronutrient during pregnancy is iron, which is important in cellular functions. While iron absorption increases in pregnancy, little is known about the exact mechanisms regulating maternal iron levels and transfer through the placenta in normal and complicated pregnancies. Methods: In this retrospective study, we investigated the regulation of maternal and placental iron availability and storage, in normotensive and pregnancies complicated by early- or late-onset PE. Methods used were analysis of clinical records, ELISA analysis on plasma samples, immunofluorescent and Prussian Blue analysis on placenta biopsies. Results: Focusing on erythroferrone (ERFE) as a new marker and hormonal regulator of iron, our results demonstrated altered maternal ERFE levels in PE. We are the first to report the expression of ERFE in trophoblasts and indicate its lower levels in early-onset PE placentas. These changes were associated with lower placental transferrin receptor 1 (TfR1) in syncytiotrophoblasts in both early- and late-onset PE. In addition, maternal plasma ERFE levels were elevated in both early- and late-onset PE and hepcidin levels reduced in early-onset PE. Unaltered maternal plasma IL-6 levels suggest mechanism other than inflammation being involved in altered iron regulation in PE pregnancy. Discussion: Our data supports a deregulation in maternal iron bioavailability in early- and late-onset PE vs normotensive pregnancies. The exact role of placental ERFE in regulating maternal-placental-fetal iron transport axis requires further investigation.
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| 2. |
- Masoumi, Zahra, et al.
(author)
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Hypoxia-induced alpha-globin expression in syncytiotrophoblasts mimics the pattern observed in preeclamptic placentas
- 2021
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:7
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Journal article (peer-reviewed)abstract
- Preeclampsia (PE) is a pregnancy disorder associated with placental dysfunction and elevated fetal hemoglobin (HbF). Early in pregnancy the placenta harbors hematopoietic stem and progenitor cells (HSPCs) and is an extramedullary source of erythropoiesis. However, globin expression is not unique to erythroid cells and can be triggered by hypoxia. To investigate the role of the placenta in increasing globin levels previously reported in PE, flow cytometry, histological and immunostaining and in situ analyses were used on placenta samples and ex vivo explant cultures. Our results indicated that in PE pregnancies, placental HSPC homing and erythropoiesis were not affected. Non-erythroid alpha-globin mRNA and protein, but not gamma-globin, were detected in syncytiotrophoblasts and stroma of PE placenta samples. Similarly, alpha-globin protein and mRNA were upregulated in normal placenta explants cultured in hypoxia. The upregulation was inde-pendent of HIF1 and NRF2, the two main candidates of globin transcription in non-erythroid cells. Our study is the first to demonstrate alpha-globin mRNA expression in syncytiotrophoblasts in PE, induced by hypoxia. However, gamma-globin was only expressed in erythrocytes. We conclude that alpha-globin, but not HbF, is expressed in placental syncytiotrophoblasts in PE and may contribute to the pathology of the disease.
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| 3. |
- Masoumi, Zahra, et al.
(author)
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Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells
- 2019
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 20:8
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Journal article (peer-reviewed)abstract
- Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and the erythroid differentiation capacity of UCB hematopoietic stem/progenitor cells (HSPCs), UCB erythroid profiles along with the transcriptome and proteome of these cells between male and female fetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC migration/homing and in vitro erythroid colony differentiation, the UCB HSPC transcriptome and the proteomic profile of the in vitro differentiated erythroid cells differed between PE vs. normotensive samples. Accordingly, despite the absence of significant differences in the UCB erythroid populations in male or female fetuses from PE or normotensive pregnancies, transcriptional changes were observed during erythropoiesis, particularly affecting male fetuses. Pathway analysis suggested deregulation in the mammalian target of rapamycin complex 1/AMP-activated protein kinase (mTORC1/AMPK) signaling pathways controlling cell cycle, differentiation, and protein synthesis. These results associate PE with transcriptional and proteomic changes in fetal HSPCs and erythroid cells that may underlie the higher erythroblast count in the UCB in PE.
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| 4. |
- Centlow, Magnus, et al.
(author)
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Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes.
- 2008
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In: Fertility and Sterility. - : Elsevier BV. - 1556-5653 .- 0015-0282. ; 90, s. 1834-1843
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To create a library enriched in cDNAs from preeclamptic placentas to print onto microarrays for placental profiling of preeclampsia (PE) and high risk pregnancies. DESIGN: Prospective study. SETTING: University women's clinic and academic research laboratory. PATIENT(S): Ten patients with PE, 5 with PE and bilateral notching, 5 with bilateral notching without PE, and 15 normotensive patients were recruited. INTERVENTION(S): Placenta and placenta bed biopsies were collected after delivery. MAIN OUTCOME MEASURE(S): Subtracted libraries of PE transcripts were produced, and cDNAs from these libraries were used to make PE-specific cDNA arrays. Results were verified quantitatively using real-time polymerase chain reaction (PCR) and histologically using in situ hybridization and immunohistochemistry. RESULT(S): Thirty genes were significantly altered in at least one group comparison. Differences in two candidate genes were confirmed using quantitative real-time PCR. Hemoglobin alpha2 and gamma transcripts were significantly overexpressed in the PE placenta. Scattered cells in the placenta and placental blood vessels were shown to express genes encoding these hemoglobin chains. CONCLUSION(S): We demonstrate increased hemoglobin production in the PE placenta. The hemoglobin may be released into the placenta blood vessel lumen. Free heme and hemoglobin are potent toxins that cause endothelial damage and inflammation.
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